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Advice on when epilepsy patients should start and stop anticonvulsant medications

One of the main presentations at the recent Irish Neurology Association (INA) Neurology Update meeting in Belfast focused on when to start and cease anticonvulsant therapy for epilepsy patients.

The presentation was delivered by Consultant Neurologist in Beaumont Hospital, Dublin, Dr Norman Delanty. According to the definition provided by Dr Delanty, “epilepsies” are a “group of brain disorders affecting individuals of all age groups, of varying and often unknown cause, characterised by recurrent unprovoked seizures, or by one unprovoked seizure but with an ‘enduring predisposition’ to further seizures. The epilepsies may have significant consequences in terms of educational, vocational, and psychosocial functioning, and physical morbidity (and potential mortality) especially in the third of patients with drug-resistant disease.”

After outlining the consequences of poorly controlled epilepsy, Dr Delanty provided further definition of what constitutes an “enduring predisposition” to epilepsy. Such a predisposition could be the result of an underlying brain dysfunction, such as a learning disability; autism; or cerebrovascular disease. It could be the result of a potentially epileptogenic lesion that can be uncovered through neuro-imaging, or epileptiform abnormalities seen on routine electroencephalogram (EEG).

Dr Delanty told delegates it should be remembered that there are many people with undiagnosed epilepsy. He also said it is important to ask whether a “first seizure” experienced by a patient is really their first seizure.

“The convulsion is often the ‘straw that breaks the camel’s back’ and brings the patient to medical attention,” according to Dr Delanty.

“Following clinical assessment, if prior unrecognised, unappreciated seizures, then the decision to start medication is usually easy.”



He said the overall risk of recurrence in those with first seizure is 35 per cent within three-to-five years.

Dr Delanty then provided a list of issues to consider when initiating or choosing an anticonvulstant medication.

Was it a seizure? Was the seizure provoked or unprovoked?

Was it the first seizure?

Are there risk factors for epilepsy?

Is there a recognisable underlying epilepsy syndrome?

What are the potential consequences of further seizures?

How urgent is treatment initiation?

Factors to consider when choosing the type of anticonvulsant are:

Evidence from clinical trials and post-marketing experience.

Epilepsy syndrome and seizure type.

Seizure severity.

Seizure density.

Age and sex.

Current (and future) reproductive intentions.

Weight.

Medication adherence considerations.

Co-morbidities.

Cognitive profile.

Cosmetic factors.

Dr Delanty said that treatment should be individualised considering the risk/benefit ratio of each option. These considerations include:

The appropriateness of drug to seizure type.

Dosage and titration regimes.

Drug-drug interactions.

Risk for adverse drug reactions.

Dr Delanty then went on to describe the value of ‘rescue therapy’, or pharmacological first aid, with medications such as buccal midazolam and clobazam.

“All or most patients and families should be prescribed and counselled about this,” according to the consultant neurologist.

He also pointed out the importance of advanced nurse practitioners with regard to patient education, who must realise that such medication needs to be taken early in the event of a seizure, while stating that that medication prescribed should be “individualised” for each patient.

Clinicians and patients need to recognise the potential side effects of anticonvulsants. These might be dose-related (dizziness; nausea; fatigue); idiosyncratic or unpredictable  (rash; tremor; blood dyscrasia); chronic due to cumulative drug exposure (weight gain/loss; mood change); teratogenic/carcinogenic effects (VPA/TPM); and adverse events due to drug interactions (CBZ/macrolides; inducers/bone loss).

Dr Delanty noted the challenge of oligo-epilepsy, which refers to the rare or uncommon occurrence of seizures in an individual over their lifetime.

Again, he stated that treatment should be individualised and that while it may be reasonable to forgo regular medication, rescue benzodiazepines were important.

With regard to stopping anti-epileptic drugs for patients on regular medication, Dr Delanty said “there are no hard and fast rules”. He said any decisions need to be based on a detailed discussion between the patient and the neurologist.

Any withdrawal off medication needs to occur “slowly”, according to Dr Delanty. It is also important to remember, he said, there is generally a 30-45 per cent chance of relapse for people who come off their medication. Consideration needs to be given of what would the consequences of a relapse be for a patient who was currently seizure free, with the impact on driving especially important.

“If the patient is not seizure free or has significant side effects on their quality-of-life, then the decision is easy or easyish,” Dr Delanty said. Such patients should be put on a non-enzyme inducing agent.

However, if the patient is seizure free and has no significant side effects and a good quality-of-life, the decision is not so easy. These patients can either be “left as is”; have their medication withdrawn slowly; or be put on a non-enzyme inducing agent.

Dr Delanty also pointed out that if a patient stops their regular anticonvulsant therapy, but needs to begin therapy again at a later date should seizure reoccur, “10 to 20 per cent will not regain easy control in this setting and may change to drug-refractory epilepsy.”

Improvement in services

Speaking to the Medical Independent (MI) after this talk, Dr Delanty said epilepsy care in Ireland has significantly improved over the last number of years.

“It needs to continue to improve,” Dr Delanty said. “This means more consultants, more nurse specialists. The difficulty is, if you ask a lot of people, I have this impression if you go into a restaurant or a bar on a Friday night and ask what is the population of the Republic of Ireland, lots of people would still say four million. It is actually five million. So you have got the increase in population, you have got an aging population. You have got the increased risk of neurological disorders as people get older, including epilepsy. And you have got more complicated and complex treatment regimes. All of that puts pressure on resources. Also for ‘difficult’ epilepsy and epilepsy in people with special needs or intellectual disability, there should be a complex epilepsy centre, like there is in England in Chalfont, or like there is in Glasgow in Scotland or like there is in most European countries. These are places where people can actually be assessed in a specific complex epilepsy centre with possibly even respite facilities for people who require them.”

Dr Delanty also referred to the promise of more precision therapy as a result of genetic testing.

“One of the ongoing advances that I’m excited about is the advent of clinical genomics and genomic testing and exome testing to try and determine the molecular cause of somebody’s epilepsy or, in the setting of a broader epilepsy with intellectual disability, the cause of the brain dysfunction. Because we now have the wherewithal to exome sequence and come up with a molecular cause. That is also beginning to go into the area of precision therapeutics where if you find a molecular cause you will be able to find the right drug for that patient.”

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